1. The Field of the Invention
The present invention relates to a powder inhaler, i.e. a device for dispensing a powdered medicament preparation by inhalation. The device is in particular a portable multiple-dose device without propellant gas, equipped with a metering member which dispenses doses from a medicament container. Moreover, the device is based on centripetal force for achieving a more effective pulverization of the powdered inhalation medicament in such a manner that the penetration of the medicament into the lungs of a patient is improved and the adhesion to the upper respiratory passages is reduced for alleviating possible side effects caused thereby.
2. The Relevant Technology
The administering of a powdered medicament preparation by inhalation from an inhaler is commonly known. Multiple-dose type powder inhalers comprising a powder container and a metering member which measures and dispenses a unit dose are also known, for example from patent publications GB 2165159, EP 0 079 478, and EP 0 166 294. In these devices, a series of dosing recesses are notched into the surface of a cylindrical metering member, and the member is disposed in a chamber of precisely the same shape. When the metering member is rotated, the dosing recesses in turn will move first to a position in alignment with the powder container for being filled and thereafter to a position in alignment with an inhalation channel, whereupon a unit dose will fall by gravity from the dosing recess into the inhalation channel. Thereafter the dose of medication is inhaled from the inhalation channel. These devices have the drawback that they make overdosing of the medicament possible by allowing the dispensing of a plurality of doses in succession into the inhalation channel, whereby a multiple dose may be drawn by one inhalation.
Inhalation devices having a metering plate movable between a filling and a dispensing position are described e.g. in patent publications WO 92/10229, U.S. Pat. Nos. 5,113,855, and 2,587,215, EP 0 546 996, WO 94/04210 and U.S. Pat. No. 5,161,524. A further example of related devices is given in WO 93/03782. However, these devices also suffer from a drawback that they make overdosing possible by allowing the dispensing of a plurality of doses into the inhalation channel.
Attempts have been made to solve this problem by using inhalers or dispensing systems in which the dosing recess will not be emptied into the inhalation channel by gravity but, instead, the dose of medication is inhaled directly from the dosing recess, such recesses having been notched into the surface of a metering member. The metering member may have the shape of a cylinder, a cone or a truncated cone, as disclosed in patent publications WO 92/00771 and WO 92/09322. Furthermore, in these devices, the metering member having the shape of a cylinder, a cone or a truncated cone is disposed in a chamber having precisely the same shape. When the metering member is rotated, the dosing recesses will move first to a position in alignment with the medicament container for filling, and then to the inhalation channel which is shaped so that the respective dosing recess will be emptied under the effect of the air flow being inhaled, and thereafter, having rotated through a full 360°, back to a position in alignment with the medicament container. The lower surface of the chamber wall may also have an emptying aperture from which any powdered medicament possibly left in the dosing recess will fall out during the rotation.
In the rotating dispensing devices described above, the distance from the filling position to the inhalation position is less than 90° of a circle arc. Since the metering member is, for purposes of metering precision, disposed within a chamber of the same shape, and since it has to be rotated through 360°, of which at least 270° are useless for the actual function of the inhaler, in these devices particles will inevitably fall onto the slide surface between the metering member and the chamber. Thereby the rotation of the highly sensitive metering member will be disturbed and may even be completely obstructed. The metering member jamming inside the chamber will hinder the functioning of the whole device. Vigorous shaking or tapping will only increase the jamming as more powder flows into the gap between the chamber and the metering member.
An improvement of the powder inhalers of the related art is suggested in EP 0 758 911. The described powder inhaler comprises a powder container, an air channel through which air is drawn via a mouthpiece, and a metering member equipped with a dosing recess, the metering member being movable in its longitudinal direction between a first position, in which the dosing recess is filled with powder coming from the container, and a second position, in which the filled dosing recess is brought into the air channel, the powder being maintained in the recess by the support of the recess bottom, and the air channel being directed to introduce the air flow into the bottom of the dosing recess during inhalation whereby the powder is released directly from the dosing recess. According to the powder inhaler of this related reference, the metering member is a metering strip which is disposed on a flat surface and moves along the flat surface. When moving between the filling and the inhalation positions, the metering strip travels over an aperture for remnants, at which time any powder possibly remaining between the metering strip and the flat surface will fall out through the aperture. This powder inhaler is still not completely satisfying for the following reasons, e.g. the inhaled air flow is directed longitudinally relative to the metering strip. In this condition both the deaggregation of the powder and the removal of the powdered medicament from the metering strip by the inhaled air flow is not efficient. Moreover, any powder possibly left after the inhalation will remain in the air channel until the metering strip again moves along the flat surface into the air channel during a subsequent inhalation process. This remaining powder could be accidentally inhaled by the patient. Furthermore, the powder remaining inside the air channel may deteriorate due to the friction between the surfaces.
As mentioned above, a further problem with respect to powder inhalers is that a sufficient deaggregation of the powder and the removal of the powdered medicament or drug from the metering member by the inhaled air flow is not satisfactory in the powder inhalers of the related art.
It is generally known that the size of medicament particles should be 1-5 microns, preferably 2-3 microns, for the best possible penetration into their destination, i.e. deep into the lungs. The most common metering device is a so-called inhalation aerosol which is quite readily capable of reaching the optimal particle size. In addition to inhalation aerosols, an increasing number of powder inhalers are presently in use as these offer certain benefits, e.g. there is no need for ozone-destroying propellants. However, a drawback of powder inhalers is that a powdered medicament issuing from the powder inhaler has a too large particle size. Thus, most of the medicine dosage coming out of inhalers is retained in upper respiratory passages which, with certain medicines, can cause serious side effects. The medicine dosages required for different inhalation medicaments vary considerably, the smallest being approximately 0.01 mg and the largest 20 mg. When small amounts of medicine are metered in powdered form, it is generally necessary to use some adjuvant or carrier, so that the sufficiently precise measuring of a dosage would be possible with the present technology. No matter if the dosage comprises just medicine or has a carrier admixed therein, the medicine dosage substantially comprises inter-adhered particles and most of these agglomerates are too large to penetrate into the lungs. As the agglomerates are released in a powder inhaler into an air flow directed into the lungs of a patient, some dispersal of these particle deposits can occur, the dispersal resulting from the formulation of a powdered medicament and the construction of an inhaler. It is known that constructions creating a strong turbulence are capable of more effective pulverization.
In practice, however, no prior known powder inhalator structure and/or medicine formulation has produced results that would be equal to those achieved by an ordinary inhalation aerosol. It has been suggested as a partial solution that inhalation should be effected with as much force as possible, whereby the turbulence and pulverization of particles would accordingly be most effective. However, a quick inhalation is difficult for a person suffering e.g. from serious asthma and, on the other hand, a quick inhalation increases the residue in upper respiratory tracts. According to studies, pulverization of agglomerates is indeed intensified but the overall benefit is marginal. Excellent Pulmonary penetration in relation to the adherence of medicament to the upper respiratory tracts has been achieved by slow inhalation, corresponding to a flow rate of approximately 30 l/min or 0.5 l/sec.
Finnish patent application No. 871000 discloses a powder inhalator which has been designed in an effort to produce a clearly defined turbulence for pulverizing agglomerations of medicine. The centrally directed deflectors inside the device or the helical chute are explained to set the air flow in a spinning motion, whereby the medicine particles entrapped in the air abrade as a result of centrifugal force against the walls of the structure as well as collide with each other with resulting pulverization. The device described in the cited application has been marketed under the trade name Turbohaler® (Draco, Sweden), and the pulverizing structure therein is, as described above, a helical chute or groove. Laboratory tests indicated that this device had a relatively good pulverization of agglomerates of medicine which, however, could still be improved and intensified. In view of the pulverization of agglomerates or accumulations of medicine, there are a few defects in this device. The helical groove has in the centre thereof an open space having less air resistance than inside the groove. Accordingly, the flow rate of air and centrifugal force on the circumference of the groove are less than theoretically possible. Since the particles advance in the groove under a force caused by air resistance and centrifugal force tends to push the particles perpendicularly to the circumferential tangent, the actual force applied to the particles is a resultant of these forces and is applied diagonally relative to the circumferential tangent. Thus, the centrifugal force resulting from the spinning motion cannot be utilized in full extent for the pulverization of accumulations. In all deflector structures according to the cited application, the particles escape from the device within a few thousandths of a second when using conventional inhalation rates of 30-90 l/min, and that is a very short time for an effective pulverization. The residence time can be prolonged, e.g. by increasing the number of helices in groove portions or the number of separate deflector structures or the length of zigzagging air flow channels, but this would complicate manufacturing and cleaning and medicine residues in the actual device would increase. After all, cleaning of the structures disclosed in the cited application is difficult.
EP 0 407 028 shows in its FIGS. 5 to 7 a vortex chamber into which an inlet tangentially directs air with a pulverized medicament. The dispersion air/medicament leaves the chamber axially at an outlet. Nothing is said about the diameter of the chamber.
FR-A-2352556 shows a cylindrical vortex chamber closed at one end, operated by the action of inhalation and having one tangential air-medicament inlet duct, an additional tangential air inlet duct and an axial outlet duct near the same end of the chamber as the inlet duct. The outlet is formed by a tube-like connection extending beyond the zone of the inlet duct and impeding the air flow. Nothing is said again about the diameter of the cylindrical chamber.
Moreover, in the device described in EP 0 477 222 a powdered medicament intended for inhalation is pulverized on the basis of a sufficiently powerful centrifugal force prior to or during inhalation. The centrifugal force is produced by the action of inhalation. A powdered medicament is entrapped in a gas flow and forced in a substantially circular or rotationally symmetrical space to such a powerful rotating motion that an effective splitting of accumulations of medicine is obtained. This is affected in a rotationally symmetrical chamber whose largest internal diameter can be 20 mm. The optimum diameter of the vortex chamber operating by the action of inhalation is 10-20 mm. If the diameter is increased, the pulverization effect deteriorates in a manner that, with a diameter of more than 30 mm, the pulverization effect is no longer significant.
From EP 0 865 302, a further powder inhaler is known which comprises a medicament container for storing a dry powdered medicament, a mouthpiece being covered by a removable protective cap, and a movable dosing slide having a dosing cavity to be placed underneath a funnel outlet of the medicament container for filling. With opening of the protective cap, the movable dosing slide with the filled dosing cavity is pushed into a shutter, and the dosing cavity is closed thereby. Upon a sufficient suction force generated by an inhalation process, a valve shield pushes away the shutter, and the dosing cavity is released in order to enable inhalation of the medicament powder. Furthermore, means are provided for enabling the return of the dosing slide only after a correctly completed inhalation process. A recording unit records the number of correctly performed inhalations and blocks the powder inhaler after a predetermined number of inhalations. Between the inlet and the outlet of the mouth-piece a labyrinthine atomiser path for powder deagglomeration is provided.